title: Effects of novel human cathepsin S inhibitors on cell migration in human cancer cells.
abstract: Elevated cathepsin S (Cat S) level is correlated with higher migration ability in tumor cells. This study investigates the inhibitory effect of novel synthetic α-ketoamide compounds on cathepsin activity and cancer cell migration. The effect of several α-ketoamide compounds on the activity of recombinant cathepsins (Cat S, Cat L and Cat K) was examined. Two highly metastatic cancer cell lines were incubated with three Cat S-specific compounds (6n, 6 w and 6r) to analyze their effect on cellular Cat S activity and cell migration. At a 100 nM concentration, compounds 6n, 6r and 6 w effectively inhibited Cat S activity. Cat S activity and cell migration were significantly reduced in CL1-3 cells after treatment with either 6n or 6 w at 5 μM. Similar results were also obtained when A2058 cells were treated with 6n. These results highlight the therapeutic potential of α-ketoamide compounds, especially 6n and 6 w, to prevent or delay cancer metastasis.
authors.affiliation: Department of Life Science, Institute of Biotechnology, National Tsing Hua University , Hsinchu , Taiwan .
authors.forename: Ju-Ying
authors.initials: JY
authors.lastname: Tsai
authors.forename: Mon-Juan
authors.initials: MJ
authors.lastname: Lee
authors.forename: Margaret Dah-Tsyr
authors.initials: MD
authors.lastname: Chang
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Wang
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Haimei
authors.initials: H
authors.lastname: Huang
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D002403:Cathepsins; C028217:cathepsin S
keywords: cysteine cathepsin; lung adenocarcinoma; melanoma; α-Ketoamides